Agents Actions, 1982 Jul, 12(3), 371 - 6 Antioxidation theory of non-steroidal anti-inflammatory drugs based upon the inhibition of luminol-enhanced chemiluminescence from the myeloperoxidase reaction; Pekoe G et al.; The action of non-steroidal anti-inflammatory drugs (NSAIDS) has been ascribed to their ability to block the reaction of arachidonate with cyclooxygenase/peroxidase, thus inhibiting the cellular production of inflammation mediators such as prostaglandins and leukotrienes . However, this and other polymorphonuclear leukocyte (PMN) peroxidases such as myeloperoxidase (MPO) would still be capable of producing destructive oxidants which contribute to inflammation . Sulindac sulfide (Clinoril sulfide) has recently been shown to scavenge oxidant products of prostaglandin cyclooxygenase/peroxidase and MPO . The MPO-H2O2-Cl- reaction is a potent antimicrobial/cytotoxic system which produces HOCl, a strong oxidant . MPO itself has the ability to oxidize drugs and cellular components, and may be the main oxidant in PMN defenses . An antioxidant/free radical scavenger action of NSAIDs against the MPO system could be a primary mechanism of their anti-inflammatory effects . Other antioxidant/free radical scavengers have anti-inflammatory effects . MPO activity has previously been quantified using chemiluminescence (CL) . In this study, NSAIDs from various classes were tested for their ability to inhibit luminol-enhanced CL from MPO . The most potent NSAIDs against MPO-CL were BW755C, phenylbutazone, indomethacin and sulindac sulfide . Salicylates and arylacetic acid derivatives, such as naproxen, also decreased MPO-CL . These drugs are also effective against CL from PMNs, of which MPO may be a main source . This effect of NSAIDs on MPO suggests that NSAIDs may impair the killing mechanism of the PMN, preventing cell destruction and release of inflammation mediators . PMN MPO appears to be a target for the antioxidant/free radical scavenging effects of NSAIDs. Lab Invest, 1982 Jul, 47(1), 5 - 18 Phagocyte-generated oxygen metabolites and cellular injury; Weiss SJ et al.; Phagocytic leukocytes are motile cells capable of inducing damage and lysis of a wide variety of biologic targets . Recent insights into the mechanisms of phagocyte-mediated destruction have derived from the observation that these cells can consume and metabolize oxygen to generate an impressive array of reactive oxygen intermediates . The role of oxygen metabolites in antimicrobial defense mechanisms has been the subject of intensive study, but only recently has attention focused on the potential importance of oxygen in phagocyte-mammalian cell interactions . In this review we will examine evidence obtained in a variety of in vitro model systems demonstrating the ability of intact phagocytes to generate oxygen metabolites capable of destroying normal or neoplastic cells . A basic understanding of the biochemistry of phagocyte-mediated oxygen-dependent events should allow us to elucidate and potentially modulate immunologic defenses against neoplastic invasion, the destruction of normal tissue in pathogenic states, and the course of the inflammatory response . The role of phagocyte-derived oxygen metabolites in microbicidal activity will not be the subject of this report, and the reader is referred to recent comprehensive reviews. Scand J Work Environ Health, 1982 Jun, 8(2), 94 - 107 Inhalation anesthetics, anticancer drugs and sterilants as chemical hazards in hospitals; Vainio H; In recent years, there has been a considerable increase in the use of chemicals (chemical sterilants and antimicrobial agents, antineoplastic drugs, and anesthetic gases) in hospitals . The possible existence of occupational health hazards has often been overlooked in light of the great advantages provided by the use of chemical agents . It appears that certain hospital sectors, such as anesthesia units, sterilizing units and oncology units, require different degrees of caution and protective measures with respect to the handling of chemicals . The scientific evidence on which recommendations should be based is, in most cases, fairly meager; until more is known about the hazards, it would be prudent to minimize the occupational exposure to chemicals in hospitals. Pharmazie, 1982 Jun, 37(6), 413 - 5 Synthesis of substituted benzamides and benzimidazoles as anthelmintic and antimicrobial agents; Charles ES et al.; The synthesis and biological activity of a series of substituted benzamides (5-8, 14-17) 3,5-dinitrobenzoic acids (12, 13, 18) and benzimidazoles (9-11, 19-21) are described . Compounds 5, 6, 7, 12 and 14 showed 40-50% clearance of Nippostrongylus brasiliensis in rats at a dose of 250 mg/kg given daily for 3 d while a few compounds inhibited the growth of various strains of bacteria and fungi. J S Afr Vet Assoc, 1982 Jun, 53(2), 103 - 6 The use of detergents and sanitizers in dairy farm sanitation--an updated perspective; Gilbert PH; Raw milk quality in South Africa is poor and standard plate counts in the millions per ml are common . This is largely due to inefficient cleaning and sanitizing of dairy equipment . The basic constituents in milk are described and various soils are classified as soluble in water, alkali, acid, solvent or surfactant or as insoluble . The importance of water quality is highlighted and the influence of mineral salts on soil deposition described . Dairy detergents are broadly classified as alkaline or acid, the former being most effective against fatty and proteinaceous soils and the latter effective against mineral salts . Typical detergent ingredients and their properties are described . Chlorine is incorporated into alkaline detergents not as a sanitizing agent, but as a peptizing agent to aid in protein soil removal . At high pH values the antimicrobial activity of chlorine is greatly diminished . The use of a daily acidified rinse (pH 3,0-5,0) is preferred to the periodic acid wash, since the acid rinse prevents mineral deposition rather than removing accumulated milkstone . All cleaning programmes follow the same fundamental steps--Pre-rinse (40-50 degrees C), wash (60-70 degrees C), rinse (pH 3,0-5,0) and sanitize (25 ppm iodine and 100 ppm chlorine) . Farms following such a programme are able to achieve Standard Plate Counts of less than 10,000/ml and coliform counts of less than 10/ml for raw milk. Laryngoscope, 1982 Jun, 92(6 Pt 1), 650 - 6 Adenotonsillar hypertrophy and upper airway obstruction in evolutionary perspective; Grundfast KM et al.; Primary care physicians have become increasingly reluctant to refer children for tonsillectomy and adenoidectomy (T and A) during the past years while antimicrobial therapy for pharyngotonsillitis and otitis media has become more common . Consequently, more children retain tonsils and adenoids throughout the childhood years . Airway compromise from adenotonsillar hypertrophy is reported in 11 cases-8 with insidious onset, 3 with acute onset . Typical symptoms occurring during sleep include snoring, snorting, enuresis and obstructive apnea . Daytime symptoms included hyponasal speech, oral respiration and morning cephalgia . Methods of assessing children with adenotonsillar hypertrophy and airway compromise included polysomnography and acoustic analysis of respiratory sounds . It appears that airway compromise from adenotonsillar hypertrophy is more common now that fewer children are undergoing T and A, is being more commonly recognized because of improved methods of assessment, or both. Ann Surg, 1982 Jun, 195(6), 721 - 5 Immediate and long-term outlook for valve replacement in acute bacterial endocarditis; Symbas PN et al.; The clinical course of 22 patients with acute endocarditis treated surgically less than six weeks after the onset of antibiotic therapy was reviewed . The aortic valve was infected in 13 patients, the mitral in six, the tricuspid in two, and one patient had both aortic and mitral valve involvement . The indications for surgical intervention before the completion of adequate antibacterial therapy included uncontrollable congestive heart failure, persistent sepsis, systemic embolization, and multiple septic pulmonary embolizations . The annulus was involved by the infectious process in five of the 13 patients with aortic valve endocarditis, in one of the two patients with tricuspid valve infection, and in none of the patients with mitral valve endocarditis . There were two surgical deaths, for a mortality of 9.1% . During the follow-up period, four patients died three months, seven months, four years, and seven years after surgery . The remaining patients have been followed up for a period of five months to 10 years . One patient has a hemodynamically insignificant paravalvular leak, and another developed paravalvular regurgitation and a false aneurysm of the left sinus of Valsalva two weeks after the initial operation . She subsequently underwent successful valve replacement and repair of the aneurysm . This study confirms that valvular replacement should be done for acute endocarditis as soon as indicated, and that the incidence of reinfection and/or the development of valvular or paravalvular problems is small even in the patients with incomplete antimicrobial therapy, whether or not the annulus is involved by the infectious process. J Clin Microbiol, 1982 Jun, 15(6), 1159 - 60 Use of potato flakes agar in clinical mycology; Rinaldi MG; A formulation comprised of commercially available potato flakes, glucose, and agar provides a medium which is inexpensive, is easily prepared, and is particularly useful for the identification of mold fungi encountered in the clinical mycology laboratory . The inclusion of appropriate antimicrobial agents results in a selective medium effective in the isolation and identification of medically important fungi. J Clin Microbiol, 1982 Jun, 15(6), 1092 - 6 Isolation of Legionella pneumophila from hospital potable water specimens: comparison of direct plating with guinea pig inoculation; Edelstein PH et al.; Eighty-five potable water samples were analyzed for the presence of Legionella pneumophila by direct plating and by guinea pig inoculation methods . Direct plating methods utilized antimicrobial-containing media with and without acid treatment of specimens before inoculation . Thirty-three specimens were culture positive for L . pneumophila by one or both techniques . A total of 14 specimens were positive for L . pneumophila by direct plating only, and 2 specimens were positive for L . pneumophila by guinea pig inoculation only . The sensitivity of direct plating is significantly greater than that of guinea pig inoculation when isolating L . pneumophila from potable water (P less than 0.01). Schweiz Med Wochenschr, 1982 May 15, 112(20), 706 - 13 {Use of drugs in a medical polyclinic}; Tigretti T et al.; The medical prescriptions of 18 house officers working at the Policlinique Universitaire de Medecine in Geneva were analyzed for a period of 17 working days and provide insight into drug therapy chosen for 2194 outpatients at 2694 consultations . These patients were prescribed an average of 1.39 drugs each or 1.13 per call . Of the 298 different drugs thus prescribed, the following were chosen most frequently (in decreasing order): Digoxin, Hygroton, Lexotanil, Metamucil, Voltaren, Aspirin, different insulins and Aldomet . Antimicrobial agents accounted for only 2.5% of all prescriptions, while vitamins and "fortifiers" represent an even lower percentage . It would be possible to limit the number of drugs, since half of the prescriptions cover 23 drugs and 90% of all prescriptions cover 119 drugs . Prescription patterns vary markedly from one subspecialty of internal medicine to another, but also between physicians working in the same field . House officers in charge of given sectors of the city (internists not working in a subspecialty) may thus prescribe between 1,83 and 2.9 drugs per patient, whereas the number of drugs chosen may vary between 81 and 134 . Some quaint individual preferences for drugs were also noted and the trend is analyzed . The data is compared with results of the few existing similar studies and offers food for thought on prescription habits, directed ultimately towards a more rational approach to drug therapy for outpatients. Am J Trop Med Hyg, 1982 May, 31(3 Pt 1), 459 - 65 Susceptibility of clinically sensitive and resistant Leishmania to pentavalent antimony in vitro; Berman JD et al.; Standard courses of pentavalent antimonials frequently fail to cure cutaneous, mucocutaneous, and visceral leishmaniasis, and characteristically fail to cure diffuse cutaneous disease . We have determined the in vitro sensitivity of clinical isolates of Leishmania to pentavalent antimony to determine if inherent drug resistance of the parasite is responsible for treatment failures in human beings . Intracellular amastigotes resulting from promastigote-initiated infection of human macrophages were exposed to pentavalent antimony for 6 days at 34.5-35 degrees C . Amastigotes from clinically sensitive simple cutaneous lesions exhibited a range of in vitro sensitivity . Four strains were greater than or equal to 90% eliminated and two strains were 70-75% eliminated in vitro by concentrations of antimony (15-20 micrograms Sb/ml), comparable to peak achievable serum levels in humans . Amastigotes from initially clinically resistant simple cutaneous lesions showed a wider range of sensitivities . Five strains were greater than or equal to 90% eliminated, but one strain was only 40% eliminated and another strain was completely insensitive in vitro . The clinically resistant diffuse cutaneous strain was 61% eliminated . The techniques described herein permit determination of the in vitro antimicrobial susceptibility of Leishmania from all major human forms of leishmaniasis . The data from this series indicate that in a minority of initially resistant cases parasite resistance to the drug may be contributing to clinical resistance, and use of non-antimonial drugs might be recommended for future therapy. Oral Surg Oral Med Oral Pathol, 1982 May, 53(5), 518 - 23 The effect of chlorhexidine gluconate irrigation on the root canal flora of freshly extracted necrotic teeth; Delany GM et al.; Forty freshly extracted teeth with necrotic pulps were endodontically treated under simulated clinical conditions . Bacteriologic samples were obtained before during, immediately after, and 24 hours after instrumentation, irrigation, and medication either with 0.2 percent chlorhexidine gluconate or with sterile saline . There was a highly significant (p less than 0.0049) reduction in microorganisms in the chlorhexidine-treated specimens after the instrumentation and irrigation procedures . Further significant reductions were noted after intracanal dressing of the teeth for 24 hours with the chlorhexidine gluconate solution . The teeth treated with saline also demonstrated a generalized decrease in flora after the biomechanical procedures . However, there was an absolute increase in numbers of microorganisms for 80 percent of the uniradicular and 50 percent of the multiradicular specimens when no intracanal, antimicrobial dressing was applied . It was concluded that chlorhexidine gluconate in a 0.2 percent solution can be an effective antimicrobial agent when used as an endodontic irrigating solution and that as an intracanal, interappointment dressing, chlorhexidine helps to further reduce bacteria remaining within the root canal system. Jpn J Antibiot, 1982 May, 35(5), 1177 - 82 {Incompatibility of cefotiam dihydrochloride in parenteral preparation by high-performance liquid chromatography}; Tanno K et al.; Change in external appearance, pH values and residual antimicrobial potency of cefotiam dihydrochloride (CTM) upon combination with infusion solutions and other injections was investigated . The combinations of CTM with bromhexine hydrochloride 2 mg/ml, 2 ml, dipyridamole 5 mg/ml, 2 ml and gabexate mesilate 100 mg/vial respectively were found to be incompatible on account of turbidity produced . As for 34 other combinations, no change in their appearance, pH and potency was observed. J Am Vet Med Assoc, 1982 Apr 15, 180(8), 908 - 9 Antimicrobial resistance in Escherichia coli strains isolated from pigs with diarrhea; Libal MC et al.; Antimicrobial sensitivities were determined for 1,037 Escherichia coli isolates cultured from the intestines of pigs with diarrhea . In vitro resistance by at least 1 isolate of E coli was demonstrated to each antimicrobial tested . Isolates from suckling pigs were more often resistant to chloramphenicol than were those from weaned pigs . Significantly more E coli from weaned pigs were resistant to kanamycin and neomycin than were those from suckling pigs . Escherichia coli that were the primary cause of diarrhea (colibacillosis isolates) were significantly more resistant to kanamycin, neomycin, and spectinomycin than were noncolibacillosis isolates . The opposite was true for ampicillin. Aust J Exp Biol Med Sci, 1982 Apr, 60(Pt 2), 187 - 90 The therapeutic effect of 16 antimicrobial agents on Cryptosporidium infection in mice; Tzipori SR et al.; The therapeutic efficiency of 16 anti-microbial agents (Ethopabate, Nicarbazin, Sulphaquinoxaline, Furaltadone, Enterolyte-N, Sulphamethazine, Trinamide, Amprol, Phenamidine, Zoaquin, Halofuginone, Salinomycin, Monensin, Emtryl, Arprinocid and Amprolium) were examined against Cryptosporidium infections in mice . The Cryptosporidium was originally isolated from a field outbreak of calf diarrhoea . The drugs neither prevented nor modified the course of the infection as compared with infected, untreated mice. Pharmazie, 1982 Apr, 37(4), 254 - 6 Synthesis and evaluation of substituted 4(3H)-quinazolone derivatives for antimicrobial and antiacetylcholinesterase activities . Part 3; Misra HK et al.; The synthesis of some new 6,8-dibromo-2-N-(N-arylcarbamoyl) carbamoylmethylthio-3-aryl-4(3H)-quinazolone derivatives is described . The synthesized derivatives were screened for their antibacterial, antifungal and antiacetylcholinesterase activities in vitro . Most of the compounds exhibited interesting antimicrobial activities . The relation between this and their chemical structure has been studied. Antimicrob Agents Chemother, 1982 Apr, 21(4), 554 - 7 Antimicrobial susceptibility of Moraxella bovis determined by agar disk diffusion and broth microdilution; Webber JJ et al.; The antimicrobial susceptibility of 84 isolates of Moraxella bovis was evaluated by the standard agar disk diffusion and broth microdilution procedures . All isolates were resistant to cloxacillin by disk diffusion, with 97% of isolates having a minimal inhibitory concentration of greater than or equal to 2 micrograms/ml . Of the hemolytic isolates, 68% were resistant to streptomycin . A high frequency of susceptibility was recorded for all other antimicrobial agents tested . Quantitative data supported the use of sulfonamides, but not tylosin, for parenteral infectious bovine keratoconjunctivitis therapy. Arch Ophthalmol, 1982 Apr, 100(4), 646 - 9 Intraocular penetration of rosoxacin in rabbits; Hulem CD et al.; Rosoxacin, a new synthetic antimicrobial agent, has a wide spectrum of activity that may prove beneficial in the treatment of ocular infections . To determine the penetration of rosoxacin into ocular tissues and serum of the rabbit after topical, subconjunctival, and intravenous (IV) administration, rosoxacin levels were measured using a microbiological assay after enzymatic digestion of the ocular tissues . Quantities of rosoxacin that should prove to be of therapeutic value were detectable in the anterior segment of the eye after topical or subconjunctival administration . Subconjunctival administration also resulted in high levels in the retina and choroid area and in the optic nerve . Low levels were detected in the retina and choroid 15 minutes following IV injection; however, no detectable levels were found in the ocular tissues after this period. J Infect Dis, 1982 Apr, 145(4), 550 - 3 Effects of temperature on antimicrobial susceptibility of bacteria; Mackowiak PA et al.; The effects of variations in temperature within the physiologic range on minimal inhibitory concentrations (MICs) and on the serum bactericidal activity of 17 different antimicrobial agents for 432 strains of bacteria were studied . Comparison of 3,053 experimental MICs performed at 41.5, 40, 38.5, 37, or 35 C with duplicate standard MICs performed at 35 C showed a progressive increase in antimicrobial activity as the temperature was raised within the experimental range . At the highest temperature (41.5 C), 17.1% of MICs were four or more times lower, 7% were eight or more times lower, and 2% were greater than or equal to 16 times lower than the standard MICs performed at 35 C . Binding to proteins in serum neither accentuated nor diminished the augmenting effect of temperature on antimicrobial activity . Comparison of serum bactericidal activity determined at 35 C and 40 C revealed similar hyperthermic augmentation of antimicrobial activity. J Allergy Clin Immunol, 1982 Apr, 69(4), 382 - 7 Chronic sinusitis in children with respiratory allergy: the role of antimicrobials; Rachelefsky GS et al.; We evaluated the role of antimicrobials in the treatment of chronic maxillary sinusitis in children with respiratory allergy . Night and day cough, nasal obstruction, rhinorrhea, postnasal seen . Eighty-four children were treated in a double-blind manner with either amoxicillin, erythromycin, trimethoprim-sulfamethoxazole, or an antihistamine decongestant (carbinoxamine maleate-pseudoephedrine HCl) . Radiographic and clinical responses were best with amoxicillin, but trimethoprim-sulfamethoxazole was an adequate alternative . This study demonstrates that allergic children with chronic sinusitis with associated chronic respiratory symptoms are likely to respond clinically and radiologically with antimicrobial treatment. J Pediatr, 1982 Apr, 100(4), 647 - 50 Pharmacology of trimethoprim-sulfamethoxazole in newborn infants; Springer C et al.; The pharmacokinetic parameters of sulfamethoxazole and trimethoprim were measured in 12 newborn infants of less than 3 days postnatal age, following a single or repeated intravenous injection . The mean half-lives for SMZ and TMP were 16.5 hours and 19.0 hours, respectively . The mean volumes of distribution were SMZ 0.48 L/kg and TMP 2.7 L/kg . The mean drug clearances were SMZ 0.65 ml/minute and TMP 3.31 ml/minute . From these data the recommended loading dose is SMZ 10 mg/kg with TMP 3 mg/kg, and the maintenance dose is SMZ 3 mg/kg with TMP 1 mg/kg twice daily . No adverse side effects were seen during treatment, and the bilirubin-binding capacity of albumin were not changed at therapeutic concentrations of the antimicrobial drugs. Med Hypotheses, 1982 Apr, 8(4), 361 - 70 Immunomodulation by antimicrobial drugs; Thong YH; That some antimicrobial drugs may have adverse effects on the immune system has been largely ignored in clinical medicine . There is now a substantial body of knowledge to indicate that the immunomodulating properties of antimicrobial drugs may have important implications in prescriptive practice . This is particularly so for patients whose immune systems have been compromised by immunosuppressive drugs or their disease processes . This paper suggests that the immunomodulating properties of antimicrobial drugs can be predicted on the basis of their modes of action on microbial cells. J Antibiot (Tokyo), 1982 Apr, 35(4), 491 - 6 Binding of {3H}tetrahydroleucomycin A3 to Escherichia coli ribosomes and the effect of 3"-O-acyl derivatives of leucomycins on the binding; Omura S et al.; The analysis of {3H}tetrahydroleucomycin A3 binding to Escherichia coli ribosomes are described . The dissociation constant for tetrahydroleucomycin A3 binding to ribosomes was 1.15 x 10(-8) M . One molecule of tetrahydroleucomycin A3 was bound to each 70 S ribosome (50 S subunit) as reported with erythromycin . The effect of leucomycins and their 3"-O-acyl derivatives on {3H}tetrahydroleucomycin A3 binding to ribosomes was examined . In general, 3"-O-acyl derivatives of leucomycins exhibited stronger antimicrobial activity against Gram-positive bacteria and weaker (or equivalent) activity against E . coli than their mother compounds . However, the affinities to ribosomes were approximately equivalent to those of the mother compounds, suggesting that Gram-positive bacterial cells are more permeable to 3"-O-acyl derivatives than to the mother compounds. Immunobiology, 1982 Apr, 161(3-4), 315 - 21 Functional active complement components secreted by guinea pig peritoneal macrophages; Brade V et al.; In our studies on complement secretion functional C1, C4, C2, C3, P, D and B were clearly identified in the same cultures . Functional assays did not allow the detection of C5 to C9 . Spontaneous C3 activation occurred at a very low level in culture supernatants . The responsible enzyme was identified as a metallo-enzyme . Upon addition of antibody-coated sheep erythrocytes (EA) to culture supernatant it was possible to induce C3 activation as indicated by the apparent formation of EAC1423 . Zymosan was also able to activate C3 in culture supernatant after addition of purified functional factor B indicating efficient cooperation of factors of the alternative pathway . Thus in this in vitro system macrophages not only provide C3 but also all factors for spontaneous and induced C3 activation . If these secretory functions reflect in vivo properties of macrophages, our results may indicate that C3 and its activating systems are most relevant for local cooperation between macrophages and the complement system in inflammation and antimicrobial defense . Therefore availability of these essential factors at any time is secured by local production. Br J Surg, 1982 Apr, 69(4), 215 - 7 Clinical trials of the efficacy and duration of antibacterial cover for elective resection in inflammatory bowel disease; Hares MM et al.; A prospective double-blind placebo controlled trial was performed to test the values of 24-h cover with metronidazole and gentamicin in 57 patients requiring elective resections for inflammatory bowel disease (phase 1) . The short term antimicrobial cover was not associated with a reduction in the incidence of postoperative sepsis . A further group of 30 patients who received metronidazole and gentamicin cover for 5 days (phase 2) was therefore studied and the results were compared with phase 1 . There was a significant reduction in the incidence of sepsis in the patients receiving 5-day postoperative antibiotic cover compared with the placebo group. Br J Vener Dis, 1982 Apr, 58(2), 117 - 20 Rosaramicin and tetracycline in the treatment of non-gonococcal urethritis . A comparison of clinical and microbiological results; Darne JF et al.; The clinical and microbiological outcome of the treatment of 94 men for uncomplicated non-gonococcal urethritis (NGU) was studied . Rosaramicin 250 mg six hourly for seven days was given to 46 men and tetracycline 250 mg six hourly for seven days to 48 men; the follow-up period was up to six weeks . Complete resolution of the clinical signs of infection was seen in 40 (87%) of the men treated with rosaramicin and in 37(77%) of those treated with tetracycline . Chlamydia trachomatis was eliminated from 17 of the 18 men treated with rosaramicin and from all of the 16 men treated with tetracycline . Ureaplasma urealyticum was eliminated from 12 of the 14 men treated with rosaramicin and from 15 of the 19 receiving tetracycline . Clinical recovery correlated well with the elimination of C trachomatis but less well with that of U urealyticum . The two antimicrobial agents were equally effective in the therapy of NGU, but gastrointestinal side effects were significantly more common in men treated with rosaramicin. J Exp Med, 1982 Apr 1, 155(4), 1108 - 19 Immunization of mice against African trypanosomiasis using anti-idiotypic antibodies; Sacks DL et al.; Anti-idiotypic (anti-Id) antibodies were raised against three protective monoclonal antibodies, each with specificity for the variable antigen type (VAT) of a clone of Trypanosoma rhodesiense . The IgG1 fractions of each were pooled and administered to BALB/c mice 3-4 wk before homologous challenge . The course of primary parasitemia was altered in 19 of 30 anti-Id-treated animals . The immunity was manifested as either: (a) complete protection, (b) reduced parasitemia, or (c) selection against parasites bearing the original VAT . The three idiotypes (Id) were found in variable levels in serum during the course of infection in control animals . However, in all anti-Id-treated mice that displayed immunity, one Id in particular (7H11) was detectable much earlier in infection and in higher levels than in control mice or anti-Id-treated, nonimmune mice . Six of nine mice treated with the anti-7H11 Id alone also displayed immunity, manifested in this case exclusively as selection against parasites bearing the original VAT . The effect was again associated with the more rapid appearance of the Id after infection . Specificity of the anti-Id-induced immunity was supported by the failure of anti-7H11 Id treatment to alter the course of infection with a heterologous clone of T . rhodesiense . To our knowledge, this is the first report of the antigen-independent induction of antimicrobial immunity using anti-Id antibodies. Appl Environ Microbiol, 1982 Apr, 43(4), 899 - 904 Comparative antimicrobial activity, in vitro and in vivo, of soft N-chloramine systems and chlorhexidine; Selk SH et al.; Antimicrobial activity of the following four new N-chloramine compounds was evaluated: two chlorinated simple amino acids, a chlorinated half-ester of succinic acid, and a chlorinated half-ester of glutaric acid . For comparison, the known bactericidal agents 3-chloro-4,4-dimethyl-2-oxazolidinone and chlorhexidine were evaluated by the same procedure . The contact germicidal efficiency screen was used to examine the in vitro bactericidal activity of all six compounds in the absence and presence of 5% horse serum or 5% Triton X-100 . The four new compounds were found to have greater germicidal activity than the other compounds tested and to exhibit low toxicity and skin irritation values . The in vivo bactericidal activity was evaluated in two studies . In the occlusion test, three of the four new compounds plus chlorhexidine diacetate were tested . The N-chloramines were significantly superior to chlorhexidine in preventing the expansion of the normal flora under occlusion . In the scrub test, a gloved-hand wash method was used to compare the antimicrobial effect of a 1% solution of the chlorinated half-ester of succinic acid in triacetin with that of a commercial germicidal hand wash containing 4% chlorhexidine gluconate . The two preparations exhibited essentially the same hand-degerming activity. Laryngoscope, 1982 Apr, 92(4), 397 - 406 Malignant external otitis: long-term (months) antimicrobial therapy; Strauss M et al.; Since Chandler's initial report in 1968 on "malignant external otitis" (MEO), this entity has been recognized in its earlier stages with increasing frequency . As a result of this, the availability of new antimicrobial agents, and the judicious use of surgery, there has been an improvement in the results of therapy . There remains, however, a subgroup of patients who continue to experience a significant mortality from this infection . A review and selected discussion of our experience with MEO from 1976 to 1979 is presented . Six patients have been diagnosed and successfully treated for MEO . They presented with problems ranging from severe otalgia to multiple cranial neuropathy . For the most part, therapy consisted of the now standard aminoglycoside and carbenicillin combination . Two of the patients were in the high mortality risk group . One of these patients developed an osteomyelitis which extended across the skull base resulting in bilateral cranial neuropathies . His therapy included surgery as well as long-term (months) outpatient treatment with tobramycin and carbenicillin with an excellent result . The second patient was treated similarly . The efficacy of this approach is discussed as well as the usefulness of radionuclide bone scanning in assessing the course and therapy of patients with MEO. Agents Actions, 1982 Apr, 12(1-2), 232 - 8 Comparison of the effects of antioxidant non-steroidal anti-inflammatory drugs against myeloperoxidase and hypochlorous acid luminol-enhanced chemiluminescence; Pekoe G et al.; The interaction of myeloperoxidase (MPO) with H2O2 and Cl- provides a potent antimicrobial/cytotoxic system for polymorphonuclear leukocytes (PMNs) . MPO-related cytotoxicity may be associated with the formation of toxic oxidant MPO intermediates, HOCl, or both . MPO itself is able to oxidize drugs and cellular components . Non-steroidal anti-inflammatory drugs (NSAIDs) able to act as antioxidant free radical scavengers have recently been shown to inhibit luminol-enhanced chemiluminescence (CL) which results from the MPO-H2O2-Cl- reaction . CL is a measure of the activity of this reaction . At that time it was not clear whether the source of CL which these NSAIDs affected was HOCl or components of the initial MPO-H2O2-Cl- reaction . A NSAID antioxidant mechanism could affect MPO oxidant intermediates and HOCl . This study compares the effects of antioxidant NSAIDs, methylprednisone and free radical scavengers against MPO-based and NaOCl-based luminol-enhanced CL . Most NSAIDs which affected both MPO and NaOCl-CL appeared to share similar mechanisms, suggesting that MPO oxidant intermediates and HOCl are susceptible to NSAID effects . However, most NSAIDs were more effective against MPO-CL . The effect of these NSAIDs against MPO-CL followed the profile of NSAIDs effective in previous studies against PMN-CL . One exception to this was methylprednisone, which has no effect on PMN or MPO-CL, yet inhibited NaOCl-CL . This and other data suggest that MPO and not HOCl-related reactions are a major source of PMN-CL . Less effective NSAIDs affected NaOCl-CL better than MPO-CL . While both HOCl and MPO oxidant intermediates may be affected by NSAIDs, it appears that MPO oxidant intermediates or MPO itself are the primary target for NSAID antioxidant free radical scavenging mechanisms . These antioxidant effects impair the major killing system of the PMN and may be NSAIDs' primary anti-inflammatory mechanism . Although our data suggests the production of superoxide anion and hydroxyl radical from the MPO-H2O2-Cl- reaction, the actual presence or involvement of these free radical species is not confirmed herein. Fed Proc, 1982 Apr, 41(6), 2206 - 11 Secretion of oxygen intermediates: role in effector functions of activated macrophages; Nathan CF; The ability of macrophages to secrete reactive oxygen intermediates, such as superoxide or hydrogen peroxide, correlates closely with their capacity to kill trypanosoma, toxoplasma, leishmania, and candida . In this sense, secretion of oxygen intermediates is a biochemical marker of macrophage activation . The close correlation between oxidative metabolism and antimicrobial activity appears to stem from the direct involvement of oxygen intermediates in the killing of the same parasites by the macrophages . Similarly, there seem to be at least three experimental settings in which oxygen intermediates play a major role in nonphagocytic lysis of tumor cells by macrophages: in the presence of phorbol myristate acetate, of antitumor antibody, or of a peroxidase derived from eosinophils . These findings direct attention to antioxidant defenses in tumor cells and parasites . The oxidation-reduction cycle of glutathione is one major pathway used by tumor cells to limit oxidative injury by macrophages and granulocytes . Thus, cytotoxicity is augmented by inhibition of glutathione reductase or glutathione peroxidase, by interruption of glutathione synthesis, or by diversion of glutathione into another pathway . On the other hand, catalase appears to play a prominent role in limiting macrophage effector function against toxoplasma. Biochim Biophys Acta, 1982 Mar 29, 696(3), 315 - 22 Equilibrium and kinetic studies on the binding of des-N-tetramethyltriostin A to DNA; Fox KR et al.; The interaction between TANDEM (a des-methyl analogue of triostin A) and poly(dA-dT) results in extension of the helix by 6.8 A for each ligand molecule bound, exactly as predicted for a bis-intercalation reaction . Cooperativity is evident in Scatchard plots for the interaction at ionic strengths of 0.2 and 1.0, where the binding constant is diminished compared to that which pertains at low salt concentrations . Binding to a natural DNA (calf thymus), already considerably weaker than binding to poly(dA-dT), is also sensitive to increased ionic strength . With a self-complementary octanucleotide d(G-G-T-A-T-A-C-C) the binding curve indicates the presence of a single des-N-tetramethyltriostin A binding site per helical fragment with a non-cooperative association constant about 6 . 10(6) M-1 . Detergent-induced dissociation of des-N-tetramethyltriostin A-poly(dA-dT) complexes results in a simple exponential decay at all levels of binding, but the time constant of decay is dependent upon the initial binding ratio . This behavior cannot directly explain the cooperativity of equilibrium binding isotherms but suggests the occurrence of relatively long-lived perturbations of the helical structure by binding of the ligand . {Ala3, Ala7}des-N-tetramethyltriostin A, which has a more flexible octapeptide ring lacking the disulphide cross-bridge, dissociates from poly(dA-dT) much faster than des-N-tetramethyltriostin A . Dissociation of des-N-tetramethyltriostin A from calf thymus DNA is more rapid than dissociation of triostin A or other quinoxaline antibiotics, which may account for its low antimicrobial activity. N Z Med J, 1982 Mar 24, 95(704), 185 - 8 General practitioner prescribing practices for childhood respiratory infection; Abbott GD et al.; Prescribing practices for respiratory infection during the first three years were studied in a birth cohort of Christchurch children . Of the 5630 consultations studied 39 percent were treated with antimicrobial therapy only, 23 percent by antimicrobials supplemented by other medication, 22 percent by other medication only and 16 received no medication . There were only 27 return consultations because of the iatrogenic effects of medication prescribed for respiratory infection and all of these involved adverse reactions to antimicrobial treatment . However, in no case did these reactions require further treatment other than withdrawing or changing the child's medication . The implications of the high rate of antimicrobial prescribing present for this sample are discussed. Schweiz Med Wochenschr, 1982 Mar 20, 112(12), 417 - 8 {Sensitivity of bacteria to chemotherapeutic agents (Zurich 1980) . Part II . Bacteria isolated from outpatients}; Kayser FH et al.; The frequency with which grampositive and gramnegative bacteria sensitive to antimicrobial agents are isolated from outpatients is reported . The data were obtained by the standardized Bauer/Kirby technique . Most of the strains examined proved to be sensitive to various betalactam antibiotics, to the tetracyclines, chloramphenicol and sulphamethoxazole/trimethoprim . Aminocyclitols were the most potent drugs . No decrease in sensitivity to standard agents was observed from 1975 to 1980 in E . coli and S . aureus, the most frequently isolated organisms. Rev Infect Dis, 1982 Mar-Apr, 4(2), 390 - 401 Interactions of rifampin and trimethoprim in vitro; Alvarez S et al.; Combination of rifampin and trimethoprim (TMP) has been suggested as a means of preventing the emergence of bacterial resistance to the individual agents and of achieving synergistic antimicrobial activity . By means of standard techniques of antimicrobial susceptibility testing, combinations of rifampin and TMP were tested against clinical isolates of a variety of aerobic bacteria . Synergism was defined as a fourfold or greater decrease in the minimal inhibitory concentration (MIC) of the more active agent in the combination . Antagonism was defined as a fourfold or greater increase in the MIC of the more active agent . No change or, at most, a twofold change was considered to represent indifference . Combinations of rifampin and TMP in ratios of 7:1, 7:2, and 1:1 demonstrated synergistic activity against 12%, 13%, and 28% of 440 isolates, respectively . Antagonism was observed in 10%, 9%, and 8% of strains tested against the above ratios . Killing curves determined with selected organisms failed to demonstrate synergistic antibacterial activity . Combinations of rifampin and TMP failed to prevent the emergence of resistance to both drugs when selected strains of various bacteria were exposed to serial, subinhibitory concentrations . Thus, synergism of rifampin and TMP was observed in only a minority of strains tested, and combination of the two agents failed to prevent the emergence of drug resistance in vitro. Antimicrob Agents Chemother, 1982 Mar, 21(3), 528 - 9 Stability of antimicrobial agents in peritoneal dialysate; Sewell DL et al.; The stability of cephapirin, gentamicin, penicillin G, nafcillin, ticarcillin, and vancomycin was tested in peritoneal dialysate at 25 degrees C for 24 h . All of the antimicrobial agents were stable except penicillin G, which lost 25% of activity over 24 h (P less than 0.01) . The once-daily preparation of drug-dialysate solution is feasible for the treatment of peritonitis in patients on continuous ambulatory peritoneal dialysis. Antimicrob Agents Chemother, 1982 Mar, 21(3), 373 - 80 Antibiotic entry into human polymorphonuclear leukocytes; Prokesch RC et al.; Since bacteria which survive within phagocytes may produce serious infection, antibiotics which inactivate these intracellular organisms are needed . To establish those factors which mediate entry of antimicrobial agents into human phagocytes, we studied the uptake of 13 radiolabeled antibiotics by peripheral blood polymorphonuclear leukocytes (PMN) . At intervals during a 2-h incubation period, antibiotic uptake by PMN was determined by means of velocity gradient centrifugation, which separates the cell-associated antibiotic from the extracellular antibiotic . Penicillin G and three cephalosporin antibiotics penetrated PMN poorly . The ratio of cellular concentration to extracellular concentration (C/E) of these drugs was less than 0.01 to 0.5 . For gentamicin and isoniazid, the C/E values were approximately 0.8 to 1.0 . Chloramphenicol, rifampin, and lincomycin, antibiotics with good lipid solubility, were concentrated twofold (C/E = 2) in PMN . Ethambutol (C/E = 5), clindamycin (C/E = 11), and two erythromycin preparations (C/E = 10 to 13) were markedly concentrated within PMN . Clindamycin uptake was rapid: greater than 70% of the total drug entry occurred within the first minute . Accumulation of clindamycin and erythromycin was an active, energy-requiring process, dependent at least in part upon glycolysis . Clindamycin entered PMN by means of an active membrane transport system which was saturable and had a high binding affinity (Km = 2 mM) and maximum velocity of uptake (Vmax = 5 nmol/45 s per 10(6) cells) . These observations, together with studies of the biological consequences of intracellular antibiotics, should lead to more effective therapy for infection due to intracellular pathogens.. Pharmazie, 1982 Mar, 37(3), 215 - 21 {Screening for antimicrobial and presumed cancerostatic plant metabolites (author's transl)}; Dornberger K et al.; 693 kinds of indigenous plants randomly selected were screened for their antimicrobial activities against 23 different test organisms (Gram-positive, Gram-negative bacteria, yeast and fungi) . The results of the testing showed that 250 (36%) kinds of the plants belonging to 72 families exhibited some level of antimicrobial action in vitro . Moreover, a microbiological prescreening program was employed in search of presumed cancerostatic plant products in crude extracts . These microbial tests based on agar diffusion techniques consist of prophage induction test and BIP test (bacteria inhibition-induction-phage inhibition) . All active components selected by these microbial models are potential inhibitors of nucleic acid metabolism . A wide variety of plants was demonstrated to exhibit interesting activities in these screening systems . The bioactivity is uniformly distributed in various order . The screening results are briefly discussed. J Pharm Sci, 1982 Mar, 71(3), 311 - 4 Synthesis and antimicrobial activity of triorganotin 5-nitro-2-furoates; Kupchik EJ et al.; Five triorganotin 5-nitro-2-furoates were synthesized by reacting 5-nitro-2-furoic acid with either the corresponding bis(triorganotin) oxide or the corresponding triorganotin hydroxide . The IR spectrum of each compound was obtained over the 4000--200-cm-1 range, and some of the bands were assigned . One compound, tri-n-butyltin 5-nitro-2-furoate, was an excellent antifungal agent, completely inhibiting the growth of six of ten test fungi at a concentration of 1 microgram/ml . The new compounds were also investigated for antibacterial activity and were especially inhibitory toward Gram-positive species . Two of the compounds completely inhibited the Gram-negative bacterium Escherichia coli at a concentration of 100 microgram/ml. Burns Incl Therm Inj, 1982 Mar, 8(4), 274 - 7 In vitro inactivation of silver sulphadiazine by the addition of cerium salts; Holder IA; Silver sulphadiazine, with and without cerium salts, was tested in an in vitro topical antimicrobial susceptibility test assay for antimicrobial activity against microorganisms isolated from burn wounds . Compared to silver sulphadiazine alone the addition of cerium to silver sulphadiazine generally reduced the diameter of the antimicrobial inhibitory zones around susceptible organisms . In addition, complete nullification of the activity of silver sulphadiazine occurred in many instances. Arch Intern Med, 1982 Mar, 142(3), 577 - 8 Flucytosine-miconazole treatment of Candida peritonitis . Its use during continuous ambulatory peritoneal dialysis; Lempert KD et al.; A case of Candida parapsilosis peritonitis occurred in a patient undergoing continuous ambulatory peritoneal dialysis (CAPD) . Treatment with oral doses of flucytosine and intravenous doses of miconazole was effective . No interruption in CAPD was necessary, and acceptable flucytosine levels were obtained in the serum and dialysate . This case and information available in the literature suggest that Candida peritonitis can be treated effectively with antimicrobial agents that are well tolerated by the patient, and removal of the dialysis catheter is not always necessary for cure. Rev Infect Dis, 1982 Mar-Apr, 4(2), 372 - 7 New analogs of trimethoprim; Then RL et al.; Possible goals and recent developments in the field of antimicrobial 2,4-diamino-5-benzylpyrimidines are discussed . Three analogs of trimethoprim--all bearing different substituents at position 4 of the benzyl moiety and one also having the methoxy groups replaced by ethoxy substituents--are characterized in some detail . These analogs exhibit physicochemical properties different from those of trimethoprim and are potent inhibitors of several dihydrofolate reductases . Because they differ from trimethoprim in lipophilicity, their in vitro activity, spectrum of activity, and pharmacokinetic properties also differ from those of trimethoprim . These differences are judged to be the reason for enhanced in vivo efficacy against several experimental infections . Distinct pharmacokinetic differences observed in dogs include a longer elimination half-life and a larger volume of distribution . These favorable properties indicate the potential value of further studies in humans. Rev Infect Dis, 1982 Mar-Apr, 4(2), 302 - 10 Antibiotic combinations in experimental infections in animals; Ernst JD et al.; The study of experimental infections has afforded the opportunity to examine the response to antimicrobial therapy in the complex milieu of living animals . This review summarizes the information gained from studies of combination antibiotic therapy for experimental endocarditis, meningitis, and other infections in which host defenses are unable to participate in effecting cure . The studies cited suggest that antibiotic combinations that yield rapid microbial killing are more effective in the treatment of these selected infections than are those combinations that do not give enhanced killing . In addition, the relevance of various methods of demonstrating antimicrobial synergy is examined, and in light of the results of treatment of experimental infections, suggestions for the applications of these methods to the evaluation of the efficacy of antibiotic combinations on infections in humans are given. Rev Infect Dis, 1982 Mar-Apr, 4(2), 282 - 93 Antibiotic synergism and antimicrobial combinations in clinical infections; Eliopoulos GM et al.; The clinical benefits of antimicrobial combinations in certain situations have been appreciated for over 30 years . Combinations of cell wall-active agents with aminoglycosides, of beta-lactams with inhibitors of beta-lactamase, and of drugs that inhibit separate steps along a critical metabolic pathway may produce an enhanced bactericidal effect . The concept that combination therapy may be advantageous when resistance to a single agent develops rapidly has been applied in the treatment of tuberculosis and in the design of regimens employing rifampin, a drug with excellent antimicrobial activity but against which resistance frequently develops . By permitting successful treatment of fungal infections with a smaller total dose of amphotericin B, combination therapy may reduce the risk of nephrotoxicity . Despite the drawbacks inherent in the use of multiple drugs, antimicrobial combinations continue to play an important role in clinical therapeutics. Mol Pharmacol, 1982 Mar, 21(2), 394 - 9 Structure-activity relationships in the ansamycins . Molecular structure and activity of 3-carbomethoxy rifamycin S; Brufani M et al.; The X-ray and NMR structural study of 3-carbomethoxy rifamycin S5 was undertaken in order to determine whether its low antimicrobial activity was related to a conformation of the molecule which was unfavorable for interaction with bacterial DNA-dependent RNA polymerase . However, the molecule assumes a conformation similar to that of the active rifamycins . Indeed the compound was found to be active on the isolated enzyme, so that its low activity on whole bacteria has to be attributed to factors affecting its penetration through the bacterial cell wall. Am J Vet Res, 1982 Mar, 43(3), 499 - 501 Transfer of drug resistance and enterotoxin production in porcine Escherichia coli strains and relationship between K88 antigen and raffinose (melitose) fermentation; de Lopez AG et al.; To obtain an indication of the frequency of drug resistance together with enterotoxin production in a select group of porcine E coli strains, those enterotoxigenic strains that were resistant to specific antimicrobial agents were mated as donors with nonenterotoxigenic E coli strains that were sensitive to these drugs as recipients . Seven of the 17 strains tested transferred drug resistance by direct mating . These 7 strains also transferred drug resistance following mobilization . The frequency of recipient conversion was increased following mobilization, as compared with the frequency of conversion resulting from direct mating . In 2 of these strains, enterotoxin production was transferred together with drug resistance . Eight strains transferred drug resistance only after mobilization, and in 2 of these, enterotoxin production was transferred simultaneously with resistance to the antimicrobial agents . In 2 of the 17 strains tested, neither transfer of drug resistance nor transfer of enterotoxin production could be achieved by direct mating or after mobilization . Thirty-nine porcine E coli strains were tested for K88 antigen production and raffinose (melitose) fermentation with a view toward determining whether raffinose fermentation could be used as a diagnostic tool for the detection of the K88 antigen . In 11 of the K88-positive strains tested, only 7 fermented raffinose . In the remaining 28 K88-negative strains, 17 fermented raffinose . Consequently no meaningful correlation existed between these 2 properties of porcine enterotoxigenic E coli strains. Mayo Clin Proc, 1982 Mar, 57(3), 149 - 54 Culture-negative endocarditis; Van Scoy RE; Etiologic factors in culture-negative endocarditis--better referred to as "apparent" culture-negative endocarditis--include (1) previous antibiotic therapy, (2) fastidious, slow-growing bacteria, (3) nonbacterial organisms, (4) right-sided endocarditis, and (5) noninfective endocarditis . Patients with apparent culture-negative endocarditis are more likely to have had prior antimicrobial therapy and to experience major emboli than are patients with endocarditis whose blood cultures are positive within 48 hours . The literature suggests that survival of patients with apparent culture-negative endocarditis is 92% if fever responds to therapy within 1 week but only 50% if they are still febrile after 1 week of therapy . Guidelines for diagnosis and therapy are outlined. Rev Infect Dis, 1982 Mar-Apr, 4(2), 579 - 85 Use of trimethoprim-sulfamethoxazole for treatment of infections in patients with cancer; Bodey GP et al.; Trimethoprim-sulfamethoxazole (TMP-SMZ) was used alone and in combination with other antimicrobial agents as treatment for infections in patients with cancer . Patients who did not respond to previous treatment with combinations of antibiotics received TMP-SMZ orally or parenterally during a total of 127 episodes of infection . The combined response rate for these two routes of administration was 49%, and the individual rates were similar for both routes . Twenty-eight infections were treated with TMP-SMZ plus tobramycin, and 75% responded after treatment with other drugs had failed . Ticarcillin plus TMP-SMZ was used as initial therapy for presumed or proved infection during 276 episodes of fever . Of 102 documented infections, 77% responded . Toxicity from TMP-SMZ was minimal. Antimicrob Agents Chemother, 1982 Mar, 21(3), 516 - 8 Agar disk diffusion for the quality control testing of Autobac elution disks; Gaydos JM et al.; The standard disk diffusion method of Bauer et al . (Am . J . Clin . Pathol . 45:493-496, 1966; National Committee for Clinical Laboratory Standards, Performance standards for antimicrobial disc susceptibility tests, approved standard ASM-2, 2nd ed., 1979) was used to monitor the potency of 16 Autobac antibiotic elution disks over an 8-month period . Results obtained by using the three recommended Autobac control strains showed excellent reproducibility . Zones sizes were all within a 5-mm range, and standard deviations ranged from 0.6 to 1.3 mm. Clin Pharm, 1982 Mar-Apr, 1(2), 135 - 40 Evaluation of new cephalosporins for prophylaxis of surgical infection; DiPiro JT et al.; The appropriate use of recently marketed cephalosporins for antimicrobial prophylaxis during surgery is discussed . New cephalosporins (cefamandole, cefoxitin, cefotaxime, moxalactam, and cefoperazone) are often substituted in situations where older, "first-generation" cephalosporins or other antimicrobials traditionally have been used . Adoption of these newer agents for routine use in prophylaxis of surgical infection has led to concerns of substantially increased costs as well as development of bacterial resistance . To date, some of the newer cephalosporins have been investigated for prophylaxis of postoperative infection in cesarean section, vaginal hysterectomy, gastrointestinal surgery, open-heart surgery, and total-hip replacement . Assessment of new cephalosporins for surgical prophylaxis should include: (1) the nature of infection with each specific type of procedure, (2) the effect of antimicrobials on prevention of infection with specific procedures, and (3) factors related to the institutional environment . For the surgical procedures listed above, newer cephalosporins either have not been studied or studies have not demonstrated a reduction in postoperative infection rates in comparisons with "first-generation" cephalosporins . Valid prophylactic uses for the newer agents may arise if comparative studies demonstrate postoperative infection rates lower than with regimens using the older cephalosporins or with other established regimens . Currently, none of the newer cephalosporins can be recommended for routine use in the prophylaxis of surgical infection. Am J Obstet Gynecol, 1982 Mar 1, 142(5), 593 - 4 Inhibiting herpes simplex virus type 2 infection in human epithelial cells by gossypol, a potent spermicidal and contraceptive agent; Wichmann K et al.; PIP: Gossypol, a male contraceptive, has an antifertility effect of 99.9% . It has also been reported to possess antiviral activities, and to inhibit herpes simplex virus infection in mice . Dorsett and Kerstine found that gossypol inactivated the infectivity of the enveloped virus parainfluenza type 3 and herpes simplex for HEp-2 carcinoma cells but had no effect on the infectivity of the nonenveloped poliovirus . The authors studied the effect of gossypol on infection by herpes simplex virus type 2 (HSV-2), the causative agent of herpes genitalis . In a series of experiments, gossypol and HSV-2 were added sequentially to confluent cultures of human amniotic epithelial cells and observed daily for cytopathic changes . No cytotoxicity was observed . Gossypol exerted a pronounced antiviral effect at 100 mcM; it totally inhibited the infection by 104 plaque-forming units (PFU); 10 mcM inhibited 100 PFU, and even 3 mcM caused some inhibition of HSV . Gossypol's antiviral effect is dose-dependent . The results clearly demonstrate the inhibitory effect of gossypol on HSV-2 infection; the doses used are comparable to or lower than the minimum effective antispermatozoal concentration of gossypol . Studies have reported the lack of toxicity of gossypol on normal cells and tissues, and its inhibiting effect on the growth of gonococci . Further studies should determine whether the antimicrobial effects of gossypol should be considered a favorable side effect in its use as a contraceptive, or whether gossypol has a value as an antiviral agent alone . J Pharm Pharmacol, 1982 Mar, 34(3), 158 - 61 A comparison of log P and molecular connectivity in the structure-activity analysis of some antimicrobial agents; Boyd JC et al.; Several congeneric series of antimicrobial agents previously studied by Hansch analysis have been investigated using molecular connectivity as the descriptor of molecular structure . In all cases connectivity gave comparable or improved correlations compared with log P, particularly where the pattern of molecular substitution was more complex . It was concluded that the use of computer-generated connectivity terms had advantages over calculated log P values in its ease of application and should be considered at least for initial screening of structure-activity data. Biochemistry, 1982 Feb 2, 21(3), 562 - 7 Lactoperoxidase-catalyzed oxidation of thiocyanate: polarographic study of the oxidation products; Pruitt KM et al.; The lactoperoxidase-catalyzed oxidation of thiocyanate (SCN-) was studied by two different polarographic techniques: direct current polarography and linear sweep voltammetry . The main oxidation product at pH 6.5, with a half-wave potential (E1/2) of -0.39 to -0.44 V, was identified as hypothiocyanite (OSCN-) ion . The E1/2 for OSCN- was not available in the literature . The identification of OSCN- was based on a close correlation between the current of the OSCN- peak and the concentration of chemically assayed OSCN- . Also the specific rates of decay of the current and that of chemically detectable OSCN- were similar, and both curves followed apparent first-order kinetics . Subsequently, the addition of a reducing agent (2-mercaptoethanol) resulted in immediate disappearance of both chemically detectable OSCN- and the OSCN- wave in the polarograms . All three components of the lactoperoxidase (LPO) system (SCN-, H2O2, and LPO) were needed to produce the OSCN- peak . Addition of excess H2O2 or H2O2-LPO to an OSCN--SCN- mixture resulted in a formation of a new peak with a characteristic peak potential (Ep) of -0.20 to -0.25 V . The generation of this new peak was associated with a simultaneous, markedly enhanced decrease of OSCN- concentration, indicating a possible reaction between H2O2 (or H2O2-LPO) and OSCN- . No equivalent reaction was obtained by the addition of buffer alone . This new peak may represent higher oxy acids of SCN- (O2SCN-, O3SCN-), formed in the oxidation of OSCN- by H2O2 or by H2O2-LPO . This type of reaction can explain why, in solutions which already contain OSCN- (e.g., in saliva), the addition of H2O2 results in the formation of highly reactive, short-lived antimicrobial products in addition to OSCN-. Urol Res, 1982 Feb, 10(1), 31 - 5 Antimicrobial substances in secretion, interstitial fluid, and tissue of normal and infected canine prostate glands; Baumueller A et al.; Seven antimicrobial substances--three basic, three acidic and one amphoteric--were given in constant infusion experiments to dogs to monitor their distribution in the prostate gland . In some of the dogs an experimental bacterial prostatitis had been induced prior to the experiments . Drug levels were measured in plasma (P1), prostatic interstitial fluid (PIF), prostatic secretion (PS) and prostatic tissue (PT) . Drug levels in PIF differed considerably from those in PS . In PS and PIF only basic substances exceeded the corresponding plasma levels . Concentrations of acidic substances in PS and PIF never exceeded the simultaneous plasma levels . In PIF the concentration of these drugs was significantly higher than in PS . Our results show that previous studies of prostatic secretion levels only were too optimistic for alkaline drugs and too pessimistic for acidic drugs. J Clin Microbiol, 1982 Feb, 15(2), 278 - 81 Evaluation of the Antibiotic Removal Device; Appleman MD et al.; A new system called an Antibiotic Removal Device (ARD), used for the removal of residual antibiotics in blood specimens, was studied in 300 patients diagnosed as clinically septic despite antimicrobial therapy . Blood specimens from these patients were processed with and without the ARD into aerobic and anaerobic media . There were 53 patients who had one or more positive blood culture bottles, for a total of 109 positive blood culture bottles . Of these 109 bottles, 33.9% were positive with ARD-processed blood in aerobic media, 24.8% with ARD-processed blood in anaerobic media, 22.9% with conventionally processed blood in aerobic media, and 18.3% with conventionally processed specimens in anaerobic media . After 6 h of incubation, 14 bottles with blood processed by the ARD and 9 bottles processed conventionally were positive; after 24 h, 48 bottles with blood processed by the ARD and 31 bottles processed conventionally were positive . The same organisms were isolated from both ARD- and conventionally processed blood, with four exceptions . The ARD system, when compared with a conventional system of blood specimen processing, significantly increased the detection of bacteremia and decreased the time required for its detection in patients clinically septic despite ongoing antimicrobial therapy. Infect Immun, 1982 Feb, 35(2), 709 - 14 Effect of hydrocortisone on macrophage response to lymphokine; Masur H et al.; To define the suppressive effects of corticosteroids on mononuclear phagocyte antiprotozoal activity, normal resident peritoneal macrophages were exposed to hydrocortisone (HC) before, during, and after in vitro activation with cell-free supernatants (lymphokines) . The presence of pharmacological concentrations of HC before or during lymphokine activation prevented normal macrophages from acquiring the capacity to either respond oxidatively to Toxoplasma gondii ingestion or to inhibit intracellular toxoplasma replication . HC had no effect, however, on the cells fully stimulated by lymphokine or on macrophages previously activated in vivo . These findings indicate that although HC does not impair the ability of activated macrophages to control intracellular protozoan infection, it does compromise the antimicrobial activity of the cell-mediated immune system by rendering normal macrophages unresponsive to lymphokine. Ann Surg, 1982 Feb, 195(2), 227 - 31 A single dose tinidazole and doxycycline prophylaxis in elective surgery of colon and rectum . A prospective controlled clinical multicenter study; Giercksky KE et al.; Antimicrobial prophylaxis with agents active against aerobic and anaerobic micro-organisms leads to a significant reduction of infectious complications following colorectal surgery . A single dose (1600 mg) of tinidazole (a nitroimidazole derivate) and doxycycline (400 mg) will provide serum and tissue values well above minimum inhibitory concentration (MIC) values for more than 24 hours . To reduce the unwanted side effects and cost of prolonged antimicrobial prophylaxis, a prospective controlled clinical multicenter study comparing the effect of a single dose before operation of tinidazole and doxycycline to five days of prophylaxis before operation in 234 patients undergoing elective colorectal surgery was undertaken . Six patients given a single dose of prophylaxis before operation (n = 118) developed infectious complication (5.1%) . Prolongation of prophylaxis before operation for four days after operation (n = 116) did not lead to any further reduction of infectious complications . A single dose of tinidazole and doxycycline before operation is a simple and effective prophylaxis against infectious complications following elective colorectal surgery. Ann Surg, 1982 Feb, 195(2), 177 - 85 Candida infections in surgical patients . Dose requirements and toxicity of amphotericin B; Solomkin JS et al.; The natural history of candidiasis in general surgical patients has been poorly documented, and the toxicity of amphotericin B is widely heralded . For these reasons therapy for candidiasis is frequently withheld in situations where antimicrobial treatment seems indicated on clinical grounds . The clinical courses of 47 general surgical patients who received amphotericin therapy for presumed Candida infection were reviewed . Nineteen patients had had solid tumors, but 12 were either localized or resected tumors . Only nine patients had received prior cancer themotherapy . Twenty-one patients were treated for fungemic disease, 10 for Candida in peritonitis fluid, and 16 for apparent colonization associated with fever and organ failure syndromes . Pre-existing renal or other organ failure was the primary determinant of survival with 4/22 survivors (18%) in patients with renal failure compared with 17/25 (78%) survivors in patients without such organ failure . In patients with serum creatinine values less than 2.5 mg/dl, amphotericin therapy was associated with a transient 30% fall in creatinine clearance and a proportionate rise in serum creatinine . Dose response curves were determined and revealed substantial sterilization of cultures in both fungemic and nonfungemic patients receiving greater than or equal to 6 mg/kg . This was confirmed by autopsy material . We suggest that in this acutely ill patient popoulation uncontrolled infection is the primary determinant of organ failure . Short-term limited dosing with amphotericin B (6-8 mg/kg total dose) in conjunction with appraisal of clinical response is adequate therapy for most presumed Candida infections . Long-term high dose therapy, such as that recommended in immuodepressed patients, is not a routine necessity. J Am Dent Assoc, 1982 Feb, 104(2), 193 - 7 The prevention of dental caries: ten years later; Carlos JP; By any standards, progress toward caries prevention has been impressive during the past decade . It is arguable that more information on the precise etiology of caries and on potential new preventive methods has been acquired during the 1970s than in any comparable period previously . Substantial advances have been made toward the understanding of the complex interaction among oral microorganisms, host resistance, and dietary substrate in the initiation and progression of a caries lesion . The various mechanisms of action of the fluoride ion have been further elucidated; vaccination against caries and a reduction in the cariogenic potential of sweet foods have both become realistic possibilities . Conspicuous successes have also been achieved in the application of existing knowledge . At least 12 million more children than in 1971 are receiving partial protection against caries through self-applied fluoride programs . Other effective preventive methods, including adhesive sealants and, possibly, antimicrobial agents, could be widely and advantageously utilized if manpower and regulatory constraints were overcome, as their scientific feasibility has, for the most part, already been demonstrated . Of course, it would be naive to predict the early disappearance of dental caries as a major health problem . This will occur only gradually, and will require a much more extensive use of preventive methods--those already available as well as those still being developed by research . Nevertheless, a major step toward the goal of caries prevention has already been taken, and there is good reason to expect even more rapid progress during the 1980s. Surgery, 1982 Feb, 91(2), 173 - 7 Mycotic aortic pseudoaneurysm with aortoenteric fistula caused by Arizona hinshawii; McIntyre KE Jr et al.; A case of bacteremic infection of a nonaneurysmal atherosclerotic infrarenal abdominal aorta by Arizona hinshawii that resulted in formation of a false aneurysm and secondary aortoduodenal fistula is reported and analyzed . Patients with bacteremia, gastroenteritis, or localized infectious processes due to Arizona species should be considered at risk for possible secondary arterial infection from transient bacteremia . In addition, patients over 50 years of age with atherosclerosis or patients with previously implanted cardiac and/or vascular prostheses who develop bacteremia or gastroenteritis because of Arizona species may be candidates for aggressive treatment with antimicrobial agents . The late diagnosis of primary arterial infections is associated with a high mortality rate, and an aggressive surgical posture is clearly indicated . Antimicrobial management should be instituted promptly in conjunction with, not in place of, aggressive surgical therapy. J Oral Pathol, 1982 Feb, 11(1), 1 - 17 Role of salivary mucins in the protection of the oral cavity; Tabak LA et al.; Mucins are the principal organic constituents of mucus, the slimy visco-elastic material that coats all mucosal surfaces . Compelling evidence suggests that they play an integral role in non-immune protection of the oral cavity . Specific protective functions include: 1) protection against desiccation and environmental insult, 2) lubrication, and 3) antimicrobial effects against potential pathogens . Biosynthesis of mucin is regulated by both intrinsic ("cooperative sequential specificity") and extrinsic ("structural modulation") controls . These controls form the basis by which mucin's structure can be modified to meet a dynamically changing biological need. Ann Intern Med, 1982 Feb, 96(2), 203 - 5 Pneumococcal polysaccharide vaccine . Recommendation of the Immunization Practices Advisory Committee; Amniotic fluid analysis for antimicrobial factors; The antimicrobial factors in amniotic fluid (AF) were analyzed in 81 women during various periods of gestation . The AF inhibited the growth of E . coli 026 when the phosphate/zinc ratio was less than 200 or iron less than or equal to 1.2 microgram/ml and unbound transferrin was greater than 40% . A heat-stable non-lysozymal phosphate insensitive cationic protein with molecular weight higher than transferrin was also found in inhibitory AF . The antimicrobial properties of AF did not correlate with absolute zinc or lysozyme levels . The AF was non-inhibitory when it contained greater than 60 +/- 5 micrograms/ml of phosphate with phosphate/zinc ratio greater than 200, iron greater than 1.2 microgram/ml and unbound transferrin was less than 40% . Amongst all criteria described, iron (P = 0.002) and unbound transferrin levels (P = 0.0005) were the most reliable and consistent all through pregnancy but others were highly reliable only during the 36th-40th week of gestation . The clinical application of these factors are being investigated. Am J Obstet Gynecol, 1982 Jan 15, 142(2), 125 - 9 Efficacy of treatment regimens for lower urogenital Chlamydia trachomatis infection in women; Bowie WR et al.; One hundred thirteen women had Chlamydia trachomatis isolated from the cervix, or urethra, or both, were treated, and followed until failure occurred or for at least 40 days after initiation of treatment . On regimens given four times daily for 7 days, failure occurred in three (8%) of 38 on tetracycline, 500 mg, in none of five on erythromycin, 500 mg, and in three (8%) of 37 on erythromycin, 250 mg . On regimens of 500 mg given four times daily for 10 days, failure occurred in none of nine on tetracycline and in one (4%) of 24 on sulfisoxazole . Erythromycin, 500 mg, was stopped because of severe side effects . Another 10 women were given a loading dose of ampicillin plus additional ampicillin for 3 to 21 days and were followed for 4 to 76 days after treatment was stopped . Only two women remained culture positive after therapy . This study demonstrates that antimicrobial regimens that are frequently given to women in North America have significant activity against C . trachomatis. Schweiz Med Wochenschr, 1982 Jan 9, 112(2), 42 - 5 {Experimental study of optimal dose interval in antibiotic therapy}; Gerber AU et al.; A postantibiotic effect (PAE) was demonstrated for various antibiotics which suppressed bacterial regrowth for at least two hours beyond the termination of a short drug exposure in vitro . Rifampin, tetracycline and erythromycin already exhibit a PAE at low concentrations . In contrast, in the case of beta-lactams high concentrations - higher than those obtained in serum during oral treatment - were needed to demonstrate a PAE of these antibiotics in vitro . The PAE phenomenon may be of clinical importance with regard to dosage regimens in antimicrobial chemotherapy. Biomed Pharmacother, 1982, 36(8-9), 393 - 5 {Medical economics and optimal antibiotic therapy}; Bergogne-Berezin E; Antibiotics account for a large proportion of pharmaceutical consumption in France and in the world . Forty years after penicillin was introduced in antimicrobial therapy, the antibiotics constitute the first pharmaceutical class in the world (gross production) with beta-lactam antibiotics at the top . The sociological and economical consequences of their development are considerable: decrease in death-rates in childhood, tuberculosis healing, life lengthening, etc.: the consequences of these improvements on health organisation and structures are difficult to evaluate in terms of economics . The drawbacks of the development of antibiotic therapy besides side-effects or toxicity, are the emergence of resistant strains as a consequence of selective pressure due to uncontrolled use of antibiotics; the expenses increase in hospitals in relation to indiscriminate use of chemotherapeutic agents . For an optimal antibiotic therapy, a rational prescription of antibiotics and a control of appropriate antibiotic usage should be developed . However, the therapeutic efficacy and patients' cure constitute the main objective of an optimal antibiotic therapy. Ann Rech Vet, 1982, 13(3), 245 - 50 {Effect of temperature on the results of the antibiotic sensitivity test performed by the diffusion method in fish pathology}; Michel C et al.; The sensitivity disk method is currently used in fish pathology to assess the efficacy of antimicrobial drugs . However, it is generally performed at temperatures lower than 37 degrees C, at which standard procedures were recommended by WHO . In order to check up the reliability of the results, selected strains and antibiotic substances were at once studied at 37 degrees C and 22 degrees C . In the last case, two readings of the zones of inhibition were done, after 24 and 48 h of incubation . Minimal inhibitory concentrations (MIC) had been determined using an agar-plate dilution method . Each association drug-bacterial strain provided three samplings of 30 measures which were compared by variance analysis and mean comparison tests . Variances did not differ, except with chloramphenicol and tetracyclines . But the mean values of the diameters significantly differed according to the incubation temperature . The variations could reach 7 to 8 mm, in any way . So, it appears that the disk method fails to allow any quantitative interpretation when performed at 22 degrees C . Consequences in diagnostic of fish diseases are stressed. Zentralbl Gynakol, 1982, 104(23), 1514 - 8 {Pharmacokinetics of antibiotics and sulfanilamides in pregnancy and labor}; Noschel H et al.; Pharmacokinetic parameters may be influenced by pregnancy and labour . A number of antibiotics and chemotherapeutics were studied by the authors who found reduction of fictitious initial concentration as well as increase of both volume of distribution and total clearance . Elimination half-life was found to be prolonged with significance only in women in labour (ampicillin) . Studies into drug concentrations and their metabolites did not provide any evidence to change of biotransformation in gravidity . Doses of antimicrobially acting chemopharmaceuticals in gravidity should be close to upper limits. Antonie Van Leeuwenhoek, 1982, 48(3), 209 - 18 Measurements of serum gentamycin levels by rapid tests; Qadri SM et al.; Gentamicin is a very useful antimicrobial agent for the treatment of serious infections caused by gram-negative bacteria . However, it's low therapeutic index and potential ototoxic and nephrotoxic side effects necessitate frequent determinations of serum concentration to assist in maintaining therapeutic levels and avoiding toxic levels . Two bioassays and a latex agglutination inhibition card (LAIC) test were evaluated to determine gentamicin levels in nearly 100 patient sera . Results were compared with a radioimmunoassay (RIA) . Two bioassays, the Bio-Monitor and the GentaSak, gave correlation coefficients of 0.987 and 0.982, respectively . The correlation coefficient for the LAIC test was 0.987 . All three tests compared well with RIA in accurately detecting gentamicin levels in patients as well as simulated sera . The LAIC test, however, was more rapid, giving results within half an hour whereas bioassays required 6--8 hours for completion . The LAIC test was also found to be more economical . It provides a suitable alternative to RIA procedures in small laboratories and for performing 'stat' tests since batching is not necessary. Padiatr Padol, 1982, 17(3), 565 - 84 {Studies on resorption of orally administered antibiotics and chemotherapeutic agents in children and its modification . 2}; Guggenbichler JP; Besides the considerable differences in the intestinal absorption of the different antibiotic classes as described in part I of this paper galenic preparations and the administration in form of a capsule -- tablet or sirup play a major role too . The particle size of antimicrobial drugs in sirup form has to be carefully selected . It should not be too small to prevent a rapid decay of the substance by gastric acid; if it is too large the dissolution of the substance is not fast enough for maximal absorption in the upper intestinal tract . Enteric coating, soluble binders, the dissolution time of a tablet are other important variables in the absorption of orally administered antibiotics . The most important influence on the resorption of orally administered antibiotics comes from the patient . Individual variations in the absorption are exceptionally high with amoxycillin . Different age groups show considerable variations in intestinal absorption which can amount to an extent of a two to threefold increase or decrease over the mean . Simultaneous administration of food or drugs have significant influences on the absorption of certain antibiotics . The pharmacokinetic investigation and bioavailability studies are done on healthy young adults . Diseases of the intestinal tract like acute diarrhea or malabsorption syndromes influence the absorption of orally administered antibiotics to a considerable extent which even renders some drugs completely ineffective . In cystic fibrosis the enteral absorption is retarded and pharmakokinetic parameters sizably altered. J Bone Joint Surg Br, 1982, 64(4), 460 - 4 The sustained release of antimicrobial drugs from bone cement . An appraisal of laboratory investigations and their significance; Bayston R et al.; The release of gentamicin sulphate, sodium fusidate and diethanolamine fusidate from Palacos and CMW cements was studied using elution and serial plate transfer tests . Further tests were made to assay the drug remaining in the cement after antibacterial activity could no longer be detected by the above methods, to detect the sustained slow release of the residual drug, and to ascertain the mechanism of release . The results confirmed that the release of gentamicin sulphate could be detected for longer from Palacos cement than from CMW cement, but the opposite was true for sodium fusidate . Little difference was found in the case of diethanolamine fusidate . Comparison of elution and serial plate transfer tests, and of results of elution in buffers of different pH, demonstrated that the test method employed had a significant effect on the results, and the omission of details of methodology from some publications made comparison and evaluation of results difficult . Varying quantities of residual drug were found in cement from which antibacterial activity could no longer be demonstrated; further tests for sustained, slow release showed that the antibiotic did not remain fixed in the cement but was released at a rate too slow to be detected in the elution and serial plate transfer tests . It is concluded that antibiotics are released from the cement by a process of diffusion, but tests to determine the mechanism of diffusion were unhelpful . The theory of diffusion of drugs through solid matrices, and the clinical implications of the experimental findings, are discussed. Rev Infect Dis, 1982 Jan-Feb, 4(1), 69 - 77 Drug-induced fever: cases seen in the evaluation of unexplained fever in a general hospital population; Young EJ et al.; This study involved cases of unexplained fever for which an infectious disease consultation was requested and for which an untoward drug reaction was thought responsible . Twelve cases that met strict criteria for drug-induced fever are presented . Antimicrobial agents were responsible for eight cases; other causes included antihypertensive and anticonvulsant drugs and allopurinol . The duration of drug administration before fever appeared was highly variable . Most patients had no history of previous drug reaction . Seven patients had fever with on other symptoms or signs that would suggest a diagnosis of drug-induced fever . Consultations are generally not requested for adverse drug reactions with more typical findings, such as skin rashes and eosinophilia; therefore, the true incidence of drug-induced fever is probably greater than indicated by the 12 definite cases seen in this general hospital during a six-year period. Mayo Clin Proc, 1982 Jan, 57(1), 10 - 4 Experimental animal endocarditis; Wright AJ et al.; The results of studies performed with animal models of experimental infective endocarditis have provided valuable information about the pathophysiology, natural history, and treatment of this infection . The Freedman rabbit model of experimental infective endocarditis is relatively simple to perform, is reproducible, and with minor modifications has become the standard model for the study of experimental endocarditis . The following are the major advantages of the Freedman model: (1) its relatively low cost and simplicity permit the study of large numbers of animals required for statistical analysis of results; (2) the model enables accurate control of the timing of the onset of infection, the administration of antimicrobial agents, and the duration of infection and treatment before the animal is killed; and (3) the experimental infection in rabbits histologically resembles the pathologic changes that occur in this infection in humans . This model has some disadvantages: (1) the artificially induced trauma to rabbit cardiac valves is different pathophysiologically from the conditions that predispose humans to infective endocarditis; (2) a larger inoculum of bacteria is required to produce infections in rabbits than that which causes human endocarditis; and (3) the rabbit model is a more severe, acute form of infection than human infective endocarditis, and survival of untreated animals for longer than 2 weeks is unusual . One should exercise considerable caution in extrapolating the results obtained from animal experimental infective endocarditis to human infection. Arch Otolaryngol, 1982 Jan, 108(1), 11 - 4 Mycobacterium fortuitum as a cause of mastoiditis and wound infection; Neitch SM et al.; Mycobacterium fortuitum is uncommonly pathogenic for man . When implicated, this organism usually infects soft-tissue structures . Therapy necessitates surgical excision and prolonged antimicrobial therapy . A patient had a mastoiditis and wound infection due to this organism . Her successful treatment included radical debridement and prolonged therapy with several antimicrobials . The necessity for including mycobacteria in the differential diagnosis of ear, nose, and throat diseases is emphasized by our experience . The complexities of management of these infections are reviewed. Ther Drug Monit, 1982, 4(2), 115 - 35 Doxycycline; Cunha BA et al.; The chemistry, mode of action, antimicrobial activity, pharmacokinetics, and therapeutic efficacy of doxycycline are reviewed . Doxycycline displays excellent activity against gram-positive and gram-negative aerobic and anaerobic pathogens . The oral absorption of doxycycline is rapid and virtually complete and is not significantly decreased by food . Moreover, serum concentrations of doxycycline following oral and intravenous (i.v.) administration are comparable . Because of the prolonged half-life of doxycycline, once daily administration is possible . Tissue penetration of doxycycline is excellent . Levels within the therapeutic range have been found in most organs and tissues, including kidney, lung, gallbladder, prostate, intestinal tract, myocardium, sinus secretions, tonsil, aqueous humor, and female reproductive tissue . Doxycycline does not accumulate in patients with renal insufficiency and is not removed from the blood to any great extent during hemodialysis . Extensive clinical investigation has shown doxycycline to be highly effective in infections of the respiratory tract, including atypical pneumonias; skin and soft tissue; genitourinary infection including gonorrhea, syphilis, nonspecific urethritis, and prostatitis; intraabdominal infection due to trauma, sepsis, or surgery; and cholera . Evidence also suggests that doxycycline will prove effective in the treatment of Legionnaires' disease . In addition, placebo-controlled clinical trials suggest doxycycline is effective in the prevention of traveler's diarrhea. Prostate, 1982, 3(2), 139 - 48 The pharmacokinetics of antibiotic diffusion in chronic bacterial prostatitis; Sharer WC et al.; Historically chronic bacterial prostatitis in the male human has been relatively resistant to antimicrobial chemotherapy . The pharmacokinetic theory of drug diffusion into the prostate is reviewed . A brief description of the various canine models utilized to quantitate antimicrobial drug diffusion is presented . Specific data concerning the diffusion of various antimicrobial agents are abstracted followed by a brief discussion of mechanistic explanations for the success or failure of drug therapy. Med Clin North Am, 1982 Jan, 66(1), 3 - 15 Principles of antibiotic therapy; Eliopoulos GM et al.; Many host factors influence both the presentation and response to therapy of clinical infections . Since the selection of an appropriate antibiotic depends significantly upon results of in vitro susceptibility testing, great care should be taken to obtain suitable specimens for culture and susceptibility studies . The likelihood that antibiotic therapy will be successful depends upon whether the drug will reach the infected site at the desired concentration and for an optimal duration of time . Local factors such as pH, oxygen tension, and the presence of inactivating substances may affect antibiotic activity . At present, many of our recommendations for dose, dosage intervals, and duration of therapy are largely empiric . Enhanced understanding of the pharmacokinetics of antimicrobial agents should provide the basis for more rational therapy in the future . The remainder of this symposium will present the data from which such recommendations can be drawn. Mayo Clin Proc, 1982 Jan, 57(1), 22 - 32 The role of the microbiology laboratory in the diagnosis and antimicrobial treatment of infective endocarditis; Washington JA 2nd; The laboratory diagnosis of infective endocarditis is based on isolation of the etiologic agent from blood cultures . Major variables affecting the yield of microorganisms include the volume of blood cultured and the number of cultures performed, the atmosphere of incubation of cultures, and the frequency of examination and subculture of blood cultures . Bactericidal tests of antibiotics, singly and in combination, are important in determining the therapeutic regimen. Med Pediatr Oncol, 1982, 10(5), 477 - 81 Spontaneous improvement of Pneumocystis carinii pneumonia in childhood acute lymphocytic leukemia; Ettinger LJ et al.; Until recently, Pneumocystis carinii pneumonitis was the most common cause of death in patients with leukemia in remission . Prior to the advent of effective antimicrobial agents, this disease was virtually 100% fatal in the cancer patient undergoing immunosuppressive therapy . The spontaneous improvement of P carinii pneumonitis in a child with acute lymphocytic leukemia suggests a higher incidence of P carinii pneumonitis in immunocompromised patients than is commonly realized. J Med Chem, 1982 Jan, 25(1), 1 - 5 Fourth Smissman Award Address . The long search for valid structure-action relationships in drugs; Albert A; In 1869, Crum Brown discovered the first structure-activity link by showing that alkaloids, even convulsive ones, were converted by N-methylation to muscle relaxants resembling curarine (itself a quaternary amine) . This led to an attempt to link every type of drug action to its own cluster of atoms . This quest was jolted when Loewi (1926) found that a quaternary amine (acetylcholine) was the principal activator of muscle! Suddenly it was seen that a chemical group could be either an agonist or antagonist, depending on its molecular setting . That the agonists were smaller molecules suggested operation of a steric factor . Moreover, Cushny (1926) had focused attention on optical enantiomers: usually only one member of each pair had biological activity, although both were identical in all other properties . The stage was now set for physical properties to play the leading role in relating structure to activity . People recalled the demonstration by Overton and Meyer (1900) that the depressant action of a drug was linked to its lipophilicity . Unhappily, further physical correlations were slow to appear . My colleagues and I, who had been studying (from 1941) the antimicrobial action of aminoacridines and hydroxyquinolines, established quantitatively the role of ionization and chelation (two electronic influences) in the action of drugs . Today most people would agree that the most important properties in determining the action of drugs are not some particular nucleus or substituent but a trio of physical properties: lipophilicity, electron distribution, and shape . Although these properties govern the activity of drugs, their selectivity is due, as I have long maintained, to another trio of properties, namely, comparative distribution (not necessarily lipophilic), comparative biochemistry, and comparative cytology. Arch Orthop Trauma Surg, 1982, 99(3), 175 - 81 Use of prophylactic antibiotics in orthopedic surgery; Surin V et al.; The use of prophylactic antibiotics was studied prospectively in 2371 consecutive clean orthopedic operations . The infection rates for operations with obvious selection for antibiotic prophylaxis were twice as high (7.2%) as compared with operations with planned prophylaxis (3.4%) and with operations without such prophylaxis (3.7%) . Sixteen per cent of all clean operations received antibiotics for prophylaxis and 85 per cent of all prophylactic courses lasted at least 8 days or longer . Fifty-one per cent of all antimicrobial drugs used during the study were administered for prophylaxis in clean orthopaedic operations . The length of the hospital stay was the only factor closely related to the length of antibiotic prophylaxis . The drugs most often used for prophylaxis were penicillinase-resistent penicillins . Significant increase of gram-negative pathogens was observed in cultures from wounds of patients on antibiotic prophylaxis. Arch Oral Biol, 1982, 27(12), 1087 - 90 Effect of diet on the colonization of the mouth by Actinomyces viscosus (T-6) in Osborne-Mendel rats; Olsson J et al.; Oral colonization by A . viscosus, strain T-6 was studied in Osborne-Mendel rats which were fed either sucrose, glucose, starch or casein alone ad libitum by mouth . Essential nutrients were given to the rats twice daily by stomach tube . All three carbohydrates supported implantation by Actinomyces to varying degrees . Implantation did not occur when the animals were fed casein . Casein did not have any antimicrobial effect on Actinomyces already established in the rat mouth; it was impossible to eliminate an established Actinomyces flora . Feeding the animals all the dietary components through the stomach tube did not result in eradication of Actinomyces from an established flora . The Actinomyces was considerably diminished when coprophagy was prevented. Ann Chir Gynaecol Suppl, 1982, 196, 3 - 9 Tissue damage caused by activated complement and granulocytes in shock lung, post perfusion lung, and after amniotic fluid embolism: ramifications for therapy; Jacob HS et al.; The complement system evolved as a beneficial antimicrobial system . However when activated during extracorporeal perfusion, as with hemodialysis or cardiopulmonary bypass, modest pulmonary dysfunction associated with granulocyte aggregation and embolization can occur . When complement activation is more massive and prolonged as with severe sepsis, trauma and acute pancreatitis or during infusions of amniotic fluid or other lipid-rich suspensions, severe pulmonary damage which we often recognize as shock lung may occur . Therapeutic ramifications of these conclusions are evident . Thus, high doses of corticosteroids (or of non-steroidal anti-inflammatory agents, such as ibuprofen--herein not discussed) have the ability to prevent aggregation and embolization of stimulated granulocytes to patent vessels downstream and also inhibit their production of toxic oxygen radicals . These beneficial properties suggest the use of these agents may be appropriate in shock states, particularly shock lung or during suspected amniotic fluid infusion . Appropriate clinical trials to substantiate this suggestion are awaited with interest. Acta Paediatr Scand Suppl, 1982, 296, 41 - 3 Effects of varying degrees of heat treatment on milk protein and its nutritional consequenses; Schmidt E; The loss of essential protein-nutrients by heat treatment of formula products has largely been eliminated by modern techniques employed by the food industry . Heat treatment of human milk reduces the biological activity of protein-like antimicrobial factors, but pasteurisation preserves most of the IgA-activity . Little is known about possible nutritional effects on low birthweight infants of heat treatment of human milk . In one study no impairment in nitrogen absorption or retention was observed. Scand J Infect Dis Suppl, 1982, 32, 169 - 72 Treatment of uncomplicated genital Chlamydia trachomatis infections in males; Lassus A et al.; The treatment of chlamydial urethritis in males depends on the susceptibility of Chlamydia trachomatis to different antimicrobial agents . Tetracyclines seem to be the drugs of choice; long-acting tetracyclines are recommended, as these are more convenient for the patient . Both lymecycline and doxycycline produce clinical and bacteriological cure in approximately 90% of cases, when used in adequate doses . Erythromycin is the alternative treatment in patients who should not be given tetracyclines . Trimethoprim/sulfamethoxazole is effective in patients with chlamydial urethritis, but it seems to be ineffective in those with Chlamydia-negative urethritis . The importance of treating sexual partners should not be overlooked. Scand J Infect Dis Suppl, 1982, 31, 41 - 7 Pathogenesis of septicaemia: aspects of cellular defence mechanisms; Hellum KB et al.; In the secondary defence line against bacterial invasion, the phagocytic cell systems serve as effector mechanisms of specific and unspecific immunity . In bacterial infections including septicaemia the outcome of the host-parasite interaction is determined by the ability of the mono- and polymorphonuclear phagocytes to recognize and kill the invading organisms in the presence of humoral and lymphocytic factors . The quantitative aspects of phagocytic deficiency is well recognized, in general and the risk of bacterial infection in a given patient is related directly to the duration of granulocytopenia and inversely to the number of circulating granulocytes . Reduced numbers of monocytes or, as in the splenectomized patient, lack of tissue macrophages may also add to increase suseptibility to infection with certain bacteria . Functional defects in phagocytosis in the presence of normal peripheral neutrophil and monocyte counts become increasingly important with the sophisticated procedures of modern medicine . In reviewing the functional capacity of the phagocytes it is convenient to consider four interrelated phases: 1) the vascular phase characterized by amrgination, adherence and diapedesis of the cells, 2) the chemotaxis of the directed movement of the cells to site of microbial invasion, 3) the phagocytosis or ingestion of microorganisms, and 4) the cellular factors involved in the killing and decomposition of the microorganisms . Enhanced susceptibility to infection has been related to defects in any of these functions, and the basic types of inborn or acquired abnormalities are reviewed . The problems of iatrogenic defects in antimicrobial host resistance may, hopefully, be reduced by an increasing knowledge in pathophysiology and the various steps involved in the cellular defence mechanisms. Acta Chir Scand Suppl, 1982, 508, 281 - 7 The contamination of missile wounds with special reference to early antimicrobial therapy; Tikka S; A total number of 64 anesthetized Finnish home bred pigs were wounded in the soft tissue of one thigh . The shooting range was 30 m and 100 m . The weapons were the Finnish M 62, the Russian AKM 47 and the American M 16 A 1 . The projectiles were their standard ammunition . Simulating typical field conditions the skin of the pigs was covered by a Finnish field uniform . The skin and the uniform were not cleaned . After trauma the anesthetized pigs were treated in a field hospital and thoroughly examined both clinically and by laboratory tests . Immediately after wounding the wounds were dressed with sterile bandages, which were not touched for 6 hours . Bensyl-penicillin, 300000 units, was administered intravenously to every second pig 1-2 hours after trauma . The wounds were debrided 6 h after wounding and biopsies of devitalized tissue were taken for quantitative bacteriological culture and histological examination . In a group of 12 pigs the specimen was taken 72 h after trauma . After penicillin administration bacterial counts were negative in all wounds but one . No significant contamination was caused by the 7.62 calibre projectiles, but after 6 hours a bacterial count of 102-104/gram of tissue was found in 20% of wounds due to 5.56 calibre shots . The infection was verified histologically . All the wounds in the 723-hour group showed heavy secondary contamination . The study shows that early antimicrobial therapy was useful especially in the case of severe and complicated soft tissue missile wounds in the pigs. Trans R Soc Trop Med Hyg, 1982, 76(4), 476 - 8 Comparative sensitivity of Naegleria fowleri to amphotericin B and amphotericin B methyl ester; Ferrante A; Data presented showed that Naegleria fowleri is much more sensitive to amphotericin B (AmB) than to amphotericin B methyl ester (AME) . In vitro, AME was effective at concentrations of 1.0 microgram/ml whereas the parent antibiotic, AmB, was effective at concentrations of 0.0125 to 0.025 microgram/ml . In vivo, AmB, at a concentration of 2.5 mg/kg/day, produced 100% survival in mice infected with N . fowleri, but AME failed to protect infected mice even at concentrations of 30 mg/kg/day . The results support previous observations with fungi which have shown that AmB is a more potent antimicrobial agent than AME. Infect Control, 1982 Jan-Feb, 3(1), 38 - 40 Perioperative prophylactic use of antibiotics in surgery: principles and practice; Shapiro M; Prophylactic use of antimicrobics represents about 30% of total hospital use of these agents . Previous studies in animal models have suggested that timing of such prophylaxis is crucial, to the extent of the existence of a "critical period" for effective administration . This phenomenon has further been shown to exist in man, in numerous double-blind, controlled clinical trials in various types of surgical wounds . On these bases, we introduced new prophylactic protocols in a university hospital, specifically directed at reducing infection in high-risk procedures . Surveillance was conducted by infection control nurses, and one antibiotic-day was the comparative unit . Infection rates were markedly diminished under these new protocols . Total usage of antimicrobial drugs also decreased by 38% over previous rates . The rationale for limiting prophylaxis to a circumscribed period was clearly demonstrated, although the exact mechanisms responsible for this effect are, as yet, unclear. Arzneimittelforschung, 1982, 32(10), 1302 - 4 Pancreatic secretion of benzylpyrimidines . Experimental studies in dogs; Vergin H et al.; The high mortality of septicaemic complications in pancreatic diseases requires the prophylactic use of suitable antimicrobial agents . Thus, the pancreatic distribution of benzylpyrimidines has been studied in dogs . After injection of 5 mg/kg followed by constant infusion of 0.5 mg/kg/h, maximum concentrations of 3.88 +/- 1.46 micrograms/ml (metioprim, MTP), 6.07 +/- 4.95 micrograms/ml (trimethoprim, TMP) and 7.78 +/- 1.84 micrograms/ml (tetroxoprim, TXP) were reached in canine pancreatic secretion . With respect to plasma, the drugs show 2.72- (MTP), 3.57- (TMP) and 4.18fold (TXP) concentrations in pancreatic secretion as can be shown by calculation of the AUC-ratios. Scand J Infect Dis Suppl, 1982, 36, 141 - 9 The last epidemic: selective decontamination in the control of mortality among radiation victims; van der Waaij D; Observations made in Hiroshima and Nagasaki have learned that at some distance from the hypocenter of an A-bomb explosion, individuals--in densely populated areas many thousands--may receive a radiation dose which could be survived practically all exposed persons provided bacterial infections by potentially pathogenic microorganisms could effectively be prevented . As a result deteriorating hygienic circumstances may soon promote the occurrence of epidemics by pathogenic bacteria in a zone surrounding the bombed area . This may be promoted by the presence of persons with a suppressed defence capacity due to (low dose) irradiation obtained during the explosion or later on by fall out . Both infections by potentially pathogenic microbes--most of endogenous origin--as well as infections by a number of different pathogenic bacterial species could effectively be prevented by selective decontamination (SD) . SD is a method of infection prophylaxis in use in neutropenic patients such as patients with acute leukaemia during remission induction therapy . SD is performed by oral treatment with colonization resistance saving antimicrobial drugs and should start within two or three days after a nuclear explosion . Suggestions are made for the organisation of large scale treatment of many thousands of persons with SD-pills while implications of the latter for the control of epidemic spread of infections among persons living in the first aid zone who have not been exposed to radiation during or after the explosion, are also mentioned. Int J Vitam Nutr Res Suppl, 1982, 23, 23 - 34 Effects of ascorbate on normal and abnormal leucocyte functions; Anderson R; The stimulatory effects of ascorbate on neutrophil motility in vitro and in vivo and lymphocyte transformation to mitogens following ingestion or intravenous injection of ascorbate have been found to be related entirely to inhibition of the autooxidative effect of the myeloperoxidase/hydrogen peroxide/halide system (MPO/H2O2/halide system) . Stimulation of neutrophil migration and lymphocyte transformation following a single intravenous injection of 1 g of ascorbate was associated with inhibition of the MPO/H2O2/halide system . The immunostimulatory activity and peroxidase inhibitory activity was related entirely to the serum ascorbate level . The relationship between inhibition of the peroxidase/h2O2/halide system and stimulation of neutrophil motility and lymphocyte mitogen-induced transformation was further established by using the horseradish peroxidase (HRP)/H2O2/halide system in vitro . Neutrophils and lymphocytes, exposed to this system, manifested markedly impaired chemotactic responsiveness and mitogen-induced transformation, respectively . However inclusion of ascorbate with the peroxidative system protected the neutrophils and lymphocytes from these inhibitory effects . Further studies in 3 patients with chronic granulomatous disease (CGD) and 10 patients with bronchial asthma suggested that ascorbate may be of value to improve the primary immunological abnormalities (neutrophil motility and antimicrobial activity) in CGD and the secondary abnormalities (neutrophil motility and lymphocyte transformation) found in some individuals with bronchial asthma. Microbiol Immunol, 1982, 26(10), 885 - 95 Mechanisms of resistance in Escherichia coli to the sideromycin antibiotic no . 216: isolation and characterization of the resistant mutants; Miyakawa S et al.; Escherichia coli easily developed resistance to a new antimicrobial agent of the sideromycin group, No . 216, by spontaneous mutation . Most of the No . 216-resistant mutants tested proved not to be cross-resistant to E . coli phages T1, T5, and o80 . On the other hand, these phage-resistant mutants were cross resistant to No . 216 . The initial site for binding of No . 216 to the sensitive cells was located, at the ton A gene product (Ton A-protein) of the outer membrane . However, unlike the phage-resistant mutants, ton A protein (78K-protein) in most No . 216-resistant mutants was intact and these mutants were possessed a particular 87K protein in the outer membrane . It is suggested that No . 216 is taken up by ton A protein and then penetrates into the cell by way of a particular transport system and that a highly mutable portion may exist in this reaction system. Prog Clin Biol Res, 1982, 108, 5 - 29 The pathophysiology of hemorrhagic shock; Collins JA; It is difficult to summarize such a complex series of problems . Both the pathophysiology of hemorrhage and the details of its treatment are far from being fully defined in spite of the inherent simplicity of the challenge involved . The questions how much, what kind, and when still apply to such fundamental issues as the fluids given for resuscitation, red cells necessary for extensive hemorrhage and the hemostatic components . We are not clear as to what, if anything, can be done to improve antibacterial and antimicrobial defense mechanisms after a major hemorrhage . There are tantalizing leads as to specific measures that can be taken to prevent other potential complications but some maneuvers that may minimize the change for one complication may worsen the chance for others . We must, of course, continue to strive to try to reduce the complications of treatment itself, which are probably small but still significant . There is certainly much yet to be learned in both the fundamental and practical spheres. Antibiotiki, 1982, 27(9), 672 - 4 {Joint action of ethonium and antibiotics on gram-positive and gram-negative microorganisms}; Gudz' OV et al.; The inhibitory effect of antibiotics and their combinations with ethonium was studied in vitro with 10 strains of Staph . aureus and 10 strains of E . coli, Sh . sonnei and Pr . morganii . Ethonium is an antimicrobial drug of the group of cationic surface-active substances . The study was performed with the method of serial dilutions in a liquid nutrient medium . It was found that under the effect of the subbacteriostatic concentrations of ethonium, sensitivity of the microorganisms to benzylpenicillin, streptomycin, levomycetin and tetracycline incr